Using enriched populations of antigen-specific T cells from guinea pigs we will radiolabel the cells with I125 or with H3 amino acids in order to isolate and characterize the T cell receptor for antigen. Cell surface immunoglobulin receptors will be analyzed with two separate objectives in mind: 1) to determine the structural basis by which a particular class of immunoglobulin can be attached to a membrane or be present in the serum. The studies will include cleavage of the molecule and peptide mapping. 2) to determine the function of different isotype-receptors. We will attempt to elucidate by studies of antibody formation and response to mitogen the possibility that one isotype (IgM) interacting with antigen results in tolerance, whereas another isotype (IgD) interacting with antigen results in induction and does so through a proteolytic mechanism. Genetic evolution and structural relationships among products of the 9th linkage group in the mouse will be further explored. The question of whether a small subunit of these molecules is beta-2 microglobulin will be investigated both at the immunological and biochemical level. Virus receptors on lymphocytes will be studied both biochemically and ultrastructurally in order to understand the basis of tropism and the initial step in viral infection of lymphocytes. BIBLIOGRAPHIC REFERENCES: Cell Surface Immunoglobulin XI. The Appearance of an IgD-Like Molecule on Murine Lymphoid Cells During Ontogeny. Ellen S. Vitetta, Ulrich Melcher, Michael McWilliams, Michael E. Lamm, Julia M. Phillips-Quagliata and Jonathan W. Uhr, J. Exp. Med. 141:206, (1975). Cell Surface Immunoglobulin XII. Localization of immunoglobulin on murine lymphocytes by scanning immunoelectronmicroscopy. Mary F. Lipscomb, Kathryn V. Holmes, Ellen S. Vitetta, U. Hammerling and J. Uhr, Eur. J. Immunol. 5:255 (1975).